Smoking is the leading preventable cause of mortality and morbidity in the United States (CDC 2005). While smoking cessation reduces health risks and disability days, women have more difficulty quitting smoking and available treatments are less successful for women than men. Understanding gender-sensitive risk factors that increase failure to stop smoking is critical for improving interventions. Depression has been identified as a risk factor for smoking, nicotine dependence, smoking cessation failure, and failure to maintain abstinence. Women demonstrate stronger relationships than men between smoking and Major Depression;therefore, depression may exert greater effects on the ability of women to stop smoking. Gender differences in the relationship of depression and smoking behavior have not been thoroughly examined using a longitudinal population-based dataset. For the current project, we are proposing to conduct a detailed investigation into gender differences in the relationship between depression and transitions in smoking and nicotine dependence through a secondary analysis of The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Wave 1 (2001-2002, n=43,093) and Wave 2 (2004-2005, n=34,653) databases. The current study will address gaps in research on depression and smoking transitions by examining multiple mood disorders related to smoking behavior (lifetime and current Major Depression, lifetime and current Dysthymia, lifetime Minor Depression), multiple forms of smoking behavior (smoking cessation, smoking relapse, nicotine dependence), and important variables that may mediate the relationship between depression and smoking cessation (stress, control, and social support). The findings of this study will have practical implications for treatment providers and may stimulate research ultimately leading to the development of gender-specific treatments for nicotine dependence. PUBLIC HEALTH RELEVANCE: Although women have a more difficult time quitting smoking, the reasons for this relationship are not well-understood. Women have higher rates of depression and smokers with depression experience difficulty quitting smoking;however, it is unclear to what extent Major Depression, Minor Depression, and Dysthymia negatively impact the ability of smokers to quit smoking and maintain abstinence and to what degree the impact of depression is more pronounced in female smokers than male. The proposed application will examine gender differences in the relationship between depression and ability to quit smoking and avoid smoking relapse.